Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men

Abstract

Context and objective: Strategies to augment pulsatile GH may be beneficial in patients with excess visceral adiposity, in whom GH secretion is reduced. The objective of this study was to determine the effects of a novel GHRH (GHRH(1-44)) analog, tesamorelin, on endogenous GH pulsatility and insulin sensitivity in healthy men.

Design, participants, and intervention: Thirteen males (mean age 45 ± 3 yr and body mass index 27.3 ± 1.2 kg/m(2)) received tesamorelin 2 mg sc once daily for 2 wk, with assessment made at baseline, after 2 wk of treatment, and after 2 wk of withdrawal.

Outcome measures: The primary end point was change in mean overnight GH as determined by overnight frequent sampling. Secondary end points included insulin-stimulated glucose uptake as measured by euglycemic hyperinsulinemic clamp; IGF-I; and GH secretion parameters, including pulse area, pulse frequency, and basal secretion.

Results: Tesamorelin treatment increased mean overnight GH (change +0.5 ± 0.1 μg/liter, P = 0.004), average log(10) GH peak area (change +0.4 ± 0.1 log(10) μg/liter, P = 0.001), and basal GH secretion (change +0.008 ± 0.003 μg/liter · min, P = 0.008). IGF-I increased by 181 ± 22 μg/liter (P < 0.0001). Neither fasting glucose (P = 0.93) nor insulin-stimulated glucose uptake (P = 0.61) was significantly affected by tesamorelin.

Conclusions: Once-daily short-term treatment with a GHRH(1-44) analog, tesamorelin, augments basal and pulsatile GH secretion. Moreover, although tesamorelin significantly increases IGF-I, peripheral insulin-stimulated glucose uptake appears to be preserved.

Figures

Figure 1

Study schema (A) and schedule of the inpatient assessments conducted at baseline, 2 wk, and 4 wk (B). QD, Every day; NPO, nil per os.

Figure 2

Effects of tesamorelin on mean overnight GH, GH basal secretion, and mean log10 GH pulse area. Error bars represent sem.

Figure 3

A representative GH profile at baseline, after 2 wk of tesamorelin treatment, and after 2 wk of withdrawal (4 wk visit).

Figure 4

Effects of tesamorelin on fasting glucose and insulin-stimulated glucose uptake (M) as measured by euglycemic hyperinsulinemic clamp. Error bars represent sem.